The recent coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 was first reported in China (December 2019) and is now prevalent across the globe. Entry of severe acute respiratory syndrome coronavirus 2 into mammalian cells requires the binding of viral Spike (S) proteins to the angiotensin-converting enzyme 2 receptor. Once entered, the S protein is primed by a specialized serine protease, transmembrane serine protease 2 in the host cell. Importantly, besides the respiratory symptoms that are consistent with other common respiratory virus infections when patients become viremic, a significant number of COVID-19 patients also develop liver comorbidities. We explored whether a specific target cell-type in the mammalian liver could be implicated in disease pathophysiology other than the general deleterious response to cytokine storms. Here, we used single-cell RNA-seq to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We analyzed ~300,000 single cells across five different (i.e., human fetal, healthy, cirrhotic, tumor, and adjacent normal) liver tissue types. This study reports on the co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 in a TROP2 + liver progenitor population. Importantly, we detected enrichment of this cell population in the cirrhotic liver when compared with tumor tissue. These results indicated that in COVID-19-associated liver dysfunction and cell death, a viral infection of TROP2 + progenitors in the liver might significantly impair liver regeneration in patients with liver cirrhosis.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, TMPRSS2, liver, scRNA-seq, Trop2, 【초록키워드】 coronavirus disease, viral infection, coronavirus, pandemic, spike, Comorbidities, angiotensin-converting enzyme 2, China, Protein, pathophysiology, single-cell RNA-seq, Patient, Respiratory virus infection, Single Cell, receptor, cell death, disease, liver dysfunction, binding, Liver cirrhosis, Deleterious, COVID-19 patient, Cytokine storms, host cell, acute respiratory syndrome, tissue, transmembrane serine protease, respiratory symptom, serine protease, liver tissue, human liver, mammalian, mammalian cell, cell population, FIVE, co-expression, prevalent, analyzed, develop, caused, globe, significantly, healthy, reported, indicated, the S protein, implicated, impair, fetal, cirrhotic liver, 【제목키워드】 RNA-Seq, progenitor,